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A combined digital droplet PCR (ddPCR)/pyrosequencing assay system was developed that demonstrated advantages applicable to multiple qualitative and quantitative molecular genetic diagnostic applications. Data for characterizing this combined approach for hematologic stem cell transplantation (HSCT) and allele quantification from graft-derived cell-free (cf) DNA in solid organ transplantation (SOT) is presented. ddPCR and pyrosequencing assays targeting 32 SNPs/markers were established. ddPCR results from 72 gDNAs of 55 patients after allogeneic HSCT and 107 plasma-cfDNAs of 25 liver transplant recipients were compared with established methods/markers, i.e. short-tandem-repeat PCR and ALT, respectively. The ddPCR results were in good agreement with the established marker. The limit of detection was 0.02 % minor allele fraction. The relationship between ddPCR and STR-PCR was linear with R2=0.98 allowing to transfer previously established clinical STR-PCR cut-offs to ddPCR; 50-fold higher sensitivity and a variation coefficient of <2 % enable the use of low DNA concentrations (e.g. pre-sorted cells). ddPCR detected liver allograft injury at least as sensitive as ALT suggesting that ddPCR is a reliable method to monitor the transplant integrity, especially when other biomarkers are lacking (e.g. kidney). Combining pyrosequencing for genotyping and ddPCR for minor allele quantification enhances sensitivity and precision for the patient after HSCT and SOT. The assay is designed for maximum flexibility. It is expected to be suitable for other applications (sample tracking, prenatal diagnostics, etc.). [ABSTRACT FROM AUTHOR]

The introduction of cardiac troponins into clinical diagnostics has not only improved diagnostic pathways for myocardial infarction but also profoundly influenced the definition of myocardial infarction. The term troponin appeared in the literature almost 60 years ago, i.e. shortly after this journal was founded. The development of cardiac troponins from proteins involved in muscle contraction, which were in the focus of few specialized research groups from physiology and biochemistry, to one of the most frequently measured protein biomarkers in medicine is a paradigmatic success story which is also reflected in almost 300 publications on the topic in this journal. From the viewpoint of biomarker development the critical success factors were medical need, timely generation of medical evidence, and the rapid development of robust and precise laboratory assays. [ABSTRACT FROM AUTHOR]

Point-of-care (POC) measurement of thyrotropin (TSH) may facilitate prompt diagnosis of thyroid dysfunction. We evaluated the analytical performance of a new POC TSH assay (Wondfo). TSH measurements were made from 730 consecutive, unselected subjects in an outpatient setting, using Wondfo in whole blood, capillary blood and serum or automated reference equipment (serum only). TSH measurements were user-independent. Total intra-and inter-assay variation (CV%) was 12.1 and 16.2%, respectively. Total CV% was 10.6–22.6% and 14.5–21.6% in serum and whole blood, respectively. Linearity was very good. Recovery rate was 97–127%. Prolongation of incubation time increased TSH results of 12% (13%) and 33% (35%) after 2 and 5 additional minutes in serum (blood), respectively. When measured simultaneously in two Wondfo devices, the slope of the regression line was 1.03 (serum) and 1.02 (blood), with Spearman's correlation of 0.99 for both. TSH measurements between Wondfo and reference correlated strongly (r=0.93–0.96), though TSH measurements were lower with Wondfo (slopes of plots of measurements made using the two devices were 0.94 [serum vs. serum]; 0.83 [whole blood vs. serum] and 0.64 [capillary blood vs. serum]). Depending on sample material, TSH in capillary blood was lower vs. whole blood (slope: 0.82) and for whole blood vs. serum (Wondfo and reference method; slope: 0.69 and 0.83). Total haemolysis, but not elevated bilirubin or lipemia, disrupted TSH measurement. The Wondfo system was straightforward to use without need for specialist technicians and demonstrated analytic performance suitable for clinical use for the diagnosis of thyroid dysfunction. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) is a hallmark of type 2 diabetes mellitus (DM). The homeostatic model assessment of insulin resistance (HOMA-IR) provides an estimate for IR from fasting glucose and insulin serum concentrations. The aim of this study was to obtain a reference interval for HOMA-IR for a specific insulin immunoassay. The Gutenberg Health Study (GHS) is a population-based, prospective, single-center cohort study in Germany with 15,030 participants aged 35–74 years. Fasting glucose, insulin, and C-peptide were available in 10,340 participants. HOMA-IR was calculated in this group and three reference subgroups with increasingly more stringent inclusion criteria. Age- and sex-dependent distributions of HOMA-IR and reference intervals were obtained. In a substudy three insulin assays were compared and HOMA-IR estimated for each assay. Among the 10,340 participants analyzed there were 6,590 non-diabetic, 2,901 prediabetic, and 849 diabetic individuals. Median (interquartile range [IQR]) HOMA-IR was 1.54 (1.13/2.19), 2.00 (1.39/2.99), and 4.00 (2.52/6.51), respectively. The most stringently selected reference group consisted of 1,065 persons. Median (IQR) HOMA-IR was 1.09 (0.85/1.42) with no significant difference between men and women. The 97.5th percentile was 2.35. There was a non-significant trend towards higher values with older age. Comparison of three immunoassays for insulin showed an unsatisfactory correlation among the assays and systematic differences in calculated HOMA-IR. We present HOMA-IR reference intervals for adults derived by more or less stringent selection criteria for the reference cohort. In addition we show that assay specific reference intervals for HOMA-IR are required. [ABSTRACT FROM AUTHOR]

One of us (EPD) got involved with the Theranos story early in 2014 and published the very first Theranos-related scientific manuscript in I CCLM i , analyzing the Theranos testing model and claiming that there were minor, if any, revolutionary concepts about their technology [[1]]. I CCLM i readers may wonder as to why we bring back an old story, the Theranos story, which peaked in intensity and interest around 2016 and then disappeared from most people's radar after the company's total collapse in 2019. [Extracted from the article]

Background: Many European laboratories offer molecular genetic analysis of the CFTR gene using a wide range of methods to identify mutations causative of cystic fibrosis (CF) and CFTR-related disorders (CFTR-RDs). Nextgeneration sequencing (NGS) strategies are widely used in diagnostic practice, and CE marking is now required for most in vitro diagnostic (IVD) tests in Europe. The aim of this multicenter study, which involved three European laboratories specialized in CF molecular analysis, was to evaluate the performance of Multiplicom's CFTR MASTR Dx kit to obtain CE-IVD certification. Methods: A total of 164 samples, previously analyzed with well-established "reference" methods for the molecular diagnosis of the CFTR gene, were selected and resequenced using the Illumina MiSeq benchtop NGS platform. Sequencing data were analyzed using two different bioinformatic pipelines. Annotated variants were then compared to the previously obtained reference data. Results and conclusions: The analytical sensitivity, specificity and accuracy rates of the Multiplicom CFTR MASTR assay exceeded 99%. Because different types of CFTR mutations can be detected in a single workflow, the CFTR MASTR assay simplifies the overall process and is consequently well suited for routine diagnostics. [ABSTRACT FROM AUTHOR]

The article presents a study on distribution of Antiphospholipid Syndrome (APS), which is the most common acquired thrombophilia. It is noted that diagnosis is based on clinical criteria and the presence of antiphospholipid antibodies (aPLs) above the 99th percentile of a reference group. It also discusses how aPLs were able to bind to anionic phospholipids, cardiolipin or phosphatidylserine.

Background: Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) utilizing triple-quadrupole instruments has been widely used for quantification of endogenous compounds, drugs or metabolites in clinical laboratories. In contrast, high-resolution mass spectrometry (HRMS) is typically used for compound identification due to its limited dynamic range. Recently HRMS instruments with enhanced linear dynamic range have become available. The aim of this study was to evaluate HRMS for fast quantitative applications in a clinical laboratory. Methods: A high throughput UPLC-TOF-MS assay for simultaneous quantification of cyclosporin A, tacrolimus, sirolimus and everolimus was developed. All immunosuppressants were analyzed as sodium adducts in TOF-only mode using an Agilent 6540 Q-TOF system. Extracted ion chromatograms of analytes and internal standards were created from full-scan data. The assay was evaluated and compared to an established LC-MS/MS assay according to CLSI recommendations. Results: The novel HRMS assay has a total run time of 3 min. The assay is linear in a clinical relevant concentration range for all four immunosupressants. Method correlations vs. established LC-MS/MS assay were between R² = 0.99 and R² = 0.97. Total coefficients of variation (CVT) ranges were 4.5%-6.4% (tacrolimus), 7.4%-8.0% (sirolimus), 8.0%-8.8% (everolimus) and 6.1%-7.4% (cyclosporine A) for three relevant concentration levels each. Conclusions: High resolution TOF-MS and LC-MS/MS show equivalent quantitative performance for monitoring of cyclosporin A, tacrolimus, sirolimus and everolimus. HRMS has the potential to replace conventional LC-MS/MS in clinical laboratories because it simplifies assay development (no optimization of fragmentations and product ions necessary) and its full-scan data can provide additional information. [ABSTRACT FROM AUTHOR]

Background: Low circulating homoarginine has been associated with adverse cardiovascular (CV) outcome and mortality in patients at risk and in the general population. The present study aimed to define plasma homoarginine reference intervals from a representative population sample to improve risk stratification between healthy individuals and individuals at risk. Methods: We determined age- and sex-specific reference intervals for circulating plasma homoarginine in a subgroup of 786 healthy participants (no CV disease or risk factors) of the Gutenberg Health Study. Homoarginine concentrations were measured using a validated liquid chromatography-tandem mass spectrometry method. Results: Median EDTA plasma homoarginine concentration was 1.88 [25th; 75th percentile, 1.47; 2.41] µmol/L, with lower concentrations in women (1.77 [1.38; 2.26] µmol/L) than in men (2.01 [1.61; 2.56] µmol/L; p < 0.001). Sex-specific 2.5th and 97.5th percentiles of reference intervals were 0.84 and 3.89 µmol/L in women and 0.98 and 4.10 µmol/L in men, respectively. Homoarginine concentrations also depended on age and single nucleotide polymorphisms related to the L-arginine:glycine amidinotransferase gene. Conclusions: We provide plasma homoarginine reference intervals in men and women of the general population. The determination of homoarginine levels might be favorable for individual risk stratification. [ABSTRACT FROM AUTHOR]

Cytologic examination of cerebrospinal fluid (CSF) is a technically simple, yet productive diagnostic procedure. The cytocentrifuge technique is the most commonly utilized method to concentrate the generally scant cellular components of CSF. There are several preanalytical and analytical pitfalls causing artefacts and making proper assessment of the CSF cell preparation more difficult or even impossible. The common cell types of CSF are lymphocytes and monocytes including their activated forms. Cytologic examination of inflammatory conditions puts emphasis on the cellular composition of CSF caused by bacterial infections compared to viral infections and noninfectious inflammatory diseases of the brain. Concerning non-neoplastic disorders, diagnosis of subarachnoidal hemorrhage is of special interest and a main field of application of CSF cytology. The cytology of neoplastic disorders encounters three typical constellations the investigator is usually confronted with: either a primary malignancy is already known and dissemination to the meninges shall be evaluated or clinical and neuroradiological findings are suggestive of neoplastic meningitis though without sufficient evidence of the primary tumor. And third, a spinal tap is performed for other reasons and malignant cells are an incidental finding. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including the optimal strategy for rule-out and rule-in of myocardial infarction, approaches for rapid decision making in medicine, and the difference between analytical and diagnostic performance of an assay.

Background: The 99th percentile of cardiac troponin levels, determined in a reference population, is accepted as threshold for diagnosis of acute myocardial infarction (AMI). However, there is no common consensus of how to define the reference population. The aim of the present study was to determine 99th percentile reference values, determined by a high-sensitivity assay (hsTnI), according to different health status and cardiovascular risk factor prevalence in a large population-based sample. Methods: Troponin I was determined using the Abbott ARCHITECT STAT highly sensitive troponin I immunoassay in 4138 participants of the Gutenberg Health Study. Results: hsTnI was detectable in 81.6% of all individuals. The 99th percentile of the overall population was 27 ng/L. Age and gender had a prominent influence on these values. Exclusion of individuals with elevated natriuretic peptide levels or cardiac abnormalities resulted in lower 99th percentile values, whereas exclusion of individuals with an impaired estimated glomerular filtration rate (eGFR) or with prevalent coronary artery disease/myocardial infarction (CAD/MI) did not result in a meaningful change. Conclusions: Troponin I, measured by a high-sensitivity assay, can be reliably detected in the vast majority of the general population. hsTnI values were dependent on age, gender as well as structural and functional cardiac abnormalities. [ABSTRACT FROM AUTHOR]

Background: The utility of HbA1c for the diagnosis of type 2 diabetes requires an accurate, precise and robust test measurement system. Currently, immunoassay and HPLC are the most popular methods for HbA1c quantification, noting however the limitations associated with some platforms, such as imprecision or interference from common hemoglobin variants. Abbott Diagnostics has introduced a fully automated direct enzymatic method for the quantification of HbA1c from whole blood on the ARCHITECT chemistry system. Methods: Here we completed a method evaluation of the ARCHITECT HbA1c enzymatic assay for imprecision, accuracy, method comparison, interference from hemoglobin variants and specimen stability. This was completed at three independent clinical laboratories in North America and Europe. Results: The total imprecision ranged from 0.5% to 2.2% CV with low and high level control materials. Around the diagnostic cut-off of 48 mmol/mol, the total imprecision was 0.6% CV. Mean bias using reference samples from IFCC and CAP ranged from -1.1 to 1.0 mmol/mol. The enzymatic assay also showed excellent agreement with HPLC methods, with slopes of 1.01 and correlation coefficients ranging from 0.984 to 0.996 compared to Menarini Adams HA-8160, Bio-Rad Variant II and Variant II Turbo instruments. Finally, no significant effect was observed for erythrocyte sedimentation or interference from common hemoglobin variants in patient samples containing heterozygous HbS, HbC, HbD, HbE, and up to 10% HbF. Conclusions: The ARCHITECT enzymatic assay for HbA1c is a robust and fully automated method that meets the performance requirements to support the diagnosis of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Reference limits are estimators for 'extreme' percentiles of the distribution of a quantitative diagnostic marker in the healthy population. In most cases, interest will be in the 90% or 95% reference intervals. The standard parametric method of determining reference limits consists of computing quantities of the form X̅± c· S. The proportion of covered values in the underlying population coincides with the specificity obtained when a measurement value falling outside the corresponding reference region is classified as diagnostically suspect. Nonparametrically, reference limits are estimated by means of so-called order statistics. In both approaches, the precision of the estimate depends on the sample size. We present computational procedures for calculating minimally required numbers of subjects to be enrolled in a reference study. The much more sophisticated concept of reference bands replacing statistical reference intervals in case of age-dependent diagnostic markers is also discussed. [ABSTRACT FROM AUTHOR]

Background: International recommendations highlight the superior value of cardiac troponins (cTns) for early diagnosis of myocardial infarction along with analytical requirements of improved precision and detectability. In this multicenter study, we investigated the analytical performance of a new high sensitive cardiac troponin I (hs-cTnI) assay and its 99th percentile upper reference limit (URL). Methods: Laboratories from nine European countries evaluated the ARCHITECT STAT high sensitive troponin I (hs-TnI) immunoassay on the ARCHITECT i2000SR/ i1000SR immunoanalyzers. Imprecision, limit of blank (LoB), limit of detection (LoD), limit of quantitation (LoQ) linearity of dilution, interferences, sample type, method comparisons, and 99th percentile URLs were evaluated in this study. Results: Total imprecision of 3.3%-8.9%, 2.0%-3.5% and 1.5%-5.2% was determined for the low, medium and high controls, respectively. The lowest cTnI concentration corresponding to a total CV of 10% was 5.6 ng/L. Common interferences, sample dilution and carryover did not affect the hs-cTnI results. Slight, but statistically significant, differences with sample type were found. Concordance between the investigated hs-cTnI assay and contemporary cTnI assay at 99th percentile cut-off was found to be 95%. TnI was detectable in 75% and 57% of the apparently healthy population using the lower (1.1 ng/L) and upper (1.9 ng/L) limit of the LoD range provided by the ARCHITECT STAT hs-TnI package insert, respectively. The 99th percentile values were gender dependent. Conclusions: The new ARCHITECT STAT hs-TnI assay with improved analytical features meets the criteria of high sensitive Tn test and will be a valuable diagnostic tool. [ABSTRACT FROM AUTHOR]

Cardiac troponins have changed our understanding of myocardial infarction profoundly during the past 20 years. In fact release of cardiac troponin into the blood has become part of the definition of myocardial infarction. Diagnostics and treatment have taken these new insights into account. The novel high-sensitive assays for cardiac troponins that are available recently clearly constitute a significant further improvement of analytical performance. In addition, the still incomplete clinical data available indicate that these assays will also further improve patient care in many ways. In summary, cardiac troponins are a great example of the potential impact of analytical performance of diagnostic tests on patient care and patient outcome. [ABSTRACT FROM AUTHOR]

Background: The use of biomarkers is firmly established for the assessment of cardiovascular disease. Emerging biomarkers such as midregional pro-atrial natriuretic peptide (MR-proANP) challenge established markers regarding risk prediction and stratification ability. The aim of the present study was to describe the distribution of a contemporary MR-proANP assay in a large population-representative sample and to evaluate the association with prevalent cardiac diseases and cardiovascular risk factors. Methods: MR-proANP was determined by the use of a contemporary commercially available assay (BRAHMS GmbH, Hennigsdorf, Germany) in a representative sample of 5000 participants from the large population-based Gutenberg Health Study. N-terminal pro B-type natriuretic peptide (NT-proBNP) was used as a comparator. Results: Mean age was 55.5±10.9 years. Coronary artery disease (CAD) was documented in 4.6%, heart failure (HF) in 1.5% of the study participants. We observed a moderate to strong correlation of the biomarkers with age, diabetes, hypertension, smoking, renal function, prevalence of CAD and HF. Males showed lower MR-proANP concentrations than females. MR-proANP showed no relevant correlation with BMI (ρ=−0.030) and CRP (ρ=0.039). Reference limits for MR-proANP representing the 95th/97.5th/99th percentile were determined for healthy individuals with 116/132/169 pmol/mL. Conclusions: The current analysis in a large population-based sample elucidates the correlations and distribution of MR-proANP. Its concentration in healthy individuals depends on prevalent cardiovascular diseases and classical risk factors. The reported population-based reference values might be useful for distinguishing between healthy and diseased individuals, thus improving risk stratification and triaging in various clinical settings. [ABSTRACT FROM AUTHOR]

In the case of suspected acute coronary syndrome and myocardial infarction positive diagnosis or exclusion strongly depend on the use of biomarkers and in particular cardiac troponins (cTn). Especially in the early phase of myocardial infarction the sensitivity of cTn assays has been unsatisfactory. This has led to the investigation of many other potential markers for the early diagnosis of myocardial infarction. In addition, several traditional markers have been advocated, e.g., myoglobin, as these were considered to be more sensitive than cTn. With the advent of high-sensitive (hs) cTn assays the value and practical use of the alternative or additional markers has to be reassessed. According to the currently available data, no single marker is superior to hs-cTn for the diagnosis of acute myocardial infarction. In particular, the notion of superior sensitivity of myoglobin compared to cTn no longer holds true. There are two protein markers, heart-type fatty acid binding protein and copeptin, and plasma free fatty acids that may increase the diagnostic value and specifically the negative predictive value when determined on admission in combination with hs-cTn. However, the incremental gain, if any, is small. Further data are needed to determine, whether these markers can in fact improve diagnosis and if they are superior to the recommended use of the relative or absolute change of hs-cTn after 3 h. [ABSTRACT FROM AUTHOR]

Background: Posaconazole is a novel antifungal drug for oral application intended especially for therapy of invasive mycoses. Due to variable gastrointestinal absorption, adverse side effects, and suspected drug-drug interactions, therapeutic drug monitoring (TDM) of posaconazole is recommended. Method: A fast ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for quantification of posaconazole with a run-time <3 min was developed and compared to a LC-MS/MS method and HPLC method with fluorescence detection. Results: During evaluation of UPLC-MS/MS, two earlier eluting peaks were observed in the MRM trace of posaconazole. This was only seen in patient samples, but not in spiked calibrator samples. Comparison with LC-MS/MS disclosed a significant bias with higher concentrations measured by LC-MS/MS, while UPLC-MS/MS showed excellent agreement with the commercially available HPLC method. In the LC-MS/MS procedure, comparably wide and left side shifted peaks were noticed. This could be ascribed to in-source fragmentation of conjugate metabolites during electrospray ionisation. Precursor and product ion scans confirmed the assumption that the additional compounds are posaconazole glucuronides. Reducing the cone voltage led to disappearance of the glucuronide peaks. Slight modification of the LC-MS/MS method enabled separation of the main interference, leading to significantly reduced deviation. Conclusions: These results highlight the necessity to reliably eliminate interference from labile drug metabolites for correct TDM results, either by sufficient separation or selective MS conditions. The presented UPLC-MS/MS method provides a reliable and fast assay for TDM of posaconazole. Clin Chem Lab Med 2010;48:1723-31. [ABSTRACT FROM AUTHOR]

Background: Fabry disease is an X-chromosomally inherited lysosomal storage disorder leading to accumulation of glycosphingolipids, mainly globotriaosylceramide (ceramide-trihexoside, Gb3). Concentrations of Gb3 in plasma and urine have been used to diagnose Fabry disease and to monitor enzyme replacement therapy with recombinant α-galactosidase. Methods: Gb3 was purified from plasma or urine by combined liquid extraction/protein precipitation and solid-phase extraction, and was detected by flow-injection analysis electrospray mass spectrometry (MS) using multi-reaction-monitoring. Calibration was performed via standard addition using C17-Gb3 as internal standard. The most abundant isoforms were monitored for calculation of total Gb3. Results: A MS-based assay for quantification of Gb3 in plasma and urine was established and validated. Intra- and inter-assay coefficient of variation (CV) of the method were ≤12%. However, at low concentrations the CV was 16%. The linear range covers roughly two orders of magnitude, down to 0.54 mg/L in plasma and 0.07 mg/L in urine. Careful adjustment of tuning parameters was necessary to obtain identical isoform intensities and quantitative results on different mass spectrometers. Gb3 concentrations in healthy controls were <4 mg/L in EDTA-plasma and <10 μg/mmol creatinine in urine. Significantly increased Gb3 concentrations were found in plasma and urine from male and female patients with Fabry disease. Conclusions: An improved MS protocol for Gb3 quantification has been developed, validated, and shown to be suitable for diagnosis and monitoring of Fabry patients. Clin Chem Lab Med 2010;48:189–98. [ABSTRACT FROM AUTHOR]

The author reflects on the alleged violations of the journal related to clinical chemistry on publishing the articles on the novel technology of laboratory diagnostics enterprise Theranos Inc. The author states that the journal required contributors to disclose relevant competing interests. The author mentions that the alleged violation is not sufficiently substantiated.

Atherosclerosis is widely regarded as a chronic inflammatory disease that develops as a consequence of entrapment of low-density lipoprotein (LDL) in the arterial intima. Native LDL lacks inflammatory properties, so the lipoprotein must undergo biochemical alterations to become atherogenic. Among several other candidates, two different concepts of lipoprotein modification are propagated, the widespread oxidation hypothesis and the less common E-LDL hypothesis, which proposes that modification of LDL occurs through the action of ubiquitous hydrolytic enzymes (enzymatically modified LDL or E-LDL) rather than oxidation. By clearly distinguishing between the initiation and progression of atherosclerotic lesion development, this article reviews comparative studies of both types of lipoprotein modification and submits a viewpoint for discussion proposing that these lipoprotein modifications do not really compete, but rather complement one another. According to this concept, E-LDL might be more important for the initiation of atherosclerosis, while oxidative modification of LDL might be more helpful for diagnosis and prognosis of the disease. Clin Chem Lab Med 2006;44:1389–94. [ABSTRACT FROM AUTHOR]

The diagnosis of myocardial damage is preferably based on measurement of the cardiac-specific troponins. However, there is an emerging need for early, specific cardiac markers. One potential candidate is the glycogen phosphorylase BB isoenzyme (GPBB). We investigated the use of a new, commercially available GPBB ELISA assay in 61 patients presenting with an acute coronary syndrome (37 acute myocardial infarction, 24 unstable angina pectoris) in comparison to established cardiac markers such as troponin T, creatine kinase isoenzyme MB (CKMB) mass, and myoglobin. Blood samples were obtained on arrival, as well as 1, 2, 3, 4, 8, 12 and 24 h later. GPBB plasma concentrations were elevated in 90.9% of patients 1 h after onset of chest pain and increased to 100% at 4–5 h. Within the first 6 h, GPBB showed the highest sensitivity (95.5–100%) and high specificity (94–96%) compared to myoglobin (85–95% sensitivity) and CKMB mass (71.4–91.3% sensitivity). As expected, troponin T showed high specificity (100%) and sensitivity >95% later in the time course (≥3 h). In un-stable angina pectoris patients, a very high rate of elevated GPBB was observed (93.9% at 3 h) compared to myoglobin (66.7%). Cardiac troponin T and CKMB were only elevated in 33.8% and 55.0% of these patients, respectively. In conclusion, GPBB is a promising marker for the early diagnosis of acute coronary syndromes and could probably act as a marker of ischemia. However, further studies on specificity and development of a fast, automated assay are necessary before GPBB can be recommended as a routine diagnostic tool. [ABSTRACT FROM AUTHOR]

An introduction to the journal is presented in which the editor discusses various reports within the issue on topics including cardiac troponins, the impact of the novel high sensitivity (hs) assays on clinical practice, and the standardization or harmonization of the assays.

The editor talks about laboratory tests of cardiac troponins cTn) and natriuretic peptides, the effects of sample matrix on cTn, and high-dose biotin supplementation.

An introduction is presented in which the editor discusses various reports within the issue on topics including the developments in quantitative polymerase chain reaction (PCR), the risk of epithelial ovarian cancer, and the assessment of novel anticoagulants.

The article discusses the development of technology by Theranos capable of enabling the measurement of numerous analyses from a single drop of blood . It mentions the information on the preventive care system in America. It also mentions the direct to- consumer (DTC) marketing of lab tests along with the regulations for diagnostic tests in the U.S.

An introduction is presented in which the editors discuss scientific publication, databases and fees for submission.

An introduction is presented in which the editor discusses various reports within the issue on topics including International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)-WorldLab, methodology in coagulation testing, and molecular diagnostics for infectious diseases.

An introduction to the journal is presented in which the editor discusses an article regarding cardiovascular markers and cardiovascular risks.

An introduction to the journal is presented in which the authors discuss the article on reference of values of brain natriuretic peptides (BNP) among newborns and infants by M. Cantinotti and colleagues and also emphasize the relevance of reference intervals in laboratory medicine.